An open repository of real-time COVID-19 indicators.

The COVID-19 pandemic presented enormous data challenges in the United States. Policy makers, epidemiological modelers, and health researchers all require up-to-date data on the pandemic and relevant public behavior, ideally at fine spatial and temporal resolution. The COVIDcast API is our attempt to fill this need: Operational since April 2020, it provides open access to both traditional public health surveillance signals (cases, deaths, and hospitalizations) and many auxiliary indicators of COVID-19 activity, such as signals extracted from deidentified medical claims data, massive online surveys, cell phone mobility data, and internet search trends. These are available at a fine geographic resolution (mostly at the county level) and are updated daily. The COVIDcast API also tracks all revisions to historical data, allowing modelers to account for the frequent revisions and backfill that are common for many public health data sources. All of the data are available in a common format through the API and accompanying R and Python software packages. This paper describes the data sources and signals, and provides examples demonstrating that the auxiliary signals in the COVIDcast API present information relevant to tracking COVID activity, augmenting traditional public health reporting and empowering research and decision-making.

Exploring neighborhoods in large metagenome assembly graphs using spacegraphcats reveals hidden sequence diversity.

Genomes computationally inferred from large metagenomic data sets are often incomplete and may be missing functionally important content and strain variation. We introduce an information retrieval system for large metagenomic data sets that exploits the sparsity of DNA assembly graphs to efficiently extract subgraphs surrounding an inferred genome. We apply this system to recover missing content from genome bins and show that substantial genomic sequence variation is present in a real metagenome. Our software implementation is available at https://github.com/spacegraphcats/spacegraphcats under the 3-Clause BSD License.

Olaratumab for advanced soft tissue sarcoma.

INTRODUCTION: Olaratumab is a humanized IgG1 monoclonal antibody that blocks the platelet-derived growth factor receptor alpha (PDGFRα). Its antagonistic behavior inhibits the receptor's tyrosine kinase activity, thereby, turning off the downstream signaling cascades responsible for soft tissue sarcoma tumorigenesis. In October 2016, olaratumab received Food and Drug Administration (FDA) approval for its use in combination with doxorubicin for treatment of advanced soft tissue sarcoma. Areas covered: This drug profile takes a comprehensive look at the clinical studies leading to FDA approval of olaratumab as well as its safety and efficacy as a front-line treatment option for sarcoma patients. The literature search was primarily conducted using PubMed. Expert commentary: The combination of olaratumab plus doxorubicin has provided a new front-line therapeutic option for soft tissue sarcoma patients. An open-label phase Ib and randomized phase II trial in patients with advanced soft tissue sarcoma demonstrated that the addition of olaratumab to doxorubicin prolonged progression-free survival by 2.5 months and overall survival by 11.8 months when compared to doxorubicin alone. Of importance, this clinically meaningful increase in overall survival did not come at the expense of a significantly greater number of toxicities. A phase III confirmatory trial (ClinicalTrials.gov Identifier NCT02451943) will be completed in 2020.

Targeted Therapy in Head and Neck Cancer: An Update on Current Clinical Developments in Epidermal Growth Factor Receptor-Targeted Therapy and Immunotherapies.

Most patients diagnosed with head and neck squamous cell carcinoma (HNSCC) will present with locally advanced disease, requiring multimodality therapy. Despite this curative approach, a significant subset of these patients will develop locoregional failure and/or distant metastases. Despite significant progress in the treatment and subsequent prognosis of locally advanced HNSCC, the prognosis of those patients with recurrent and/or metastatic (R/M) HNSCC is poor, with short-lived responses to palliative chemotherapy and few therapeutic agents available. The discovery of the integral role of epidermal growth factor receptor overexpression in the pathogenesis of HNSCC, coupled with emerging data on the role of tumor evasion of the immune system, has opened new pathways in the development of novel therapeutic agents for the treatment of R/M HNSCC. As a result, cetuximab, a monoclonal antibody targeting epidermal growth factor receptor, as well as pembrolizumab and nivolumab, monoclonal antibodies targeting programmed cell death 1 (PD-1), are now US Food and Drug Administration approved for the treatment of R/M HNSCC. This review will detail the data supporting the use of these agents, as well as clinical trials evaluating the efficacy of other novel and promising drugs.

Brucellosis Transmission between Wildlife and Livestock in the Greater Yellowstone Ecosystem: Inferences from DNA Genotyping.

The wildlife of the Greater Yellowstone Ecosystem carries brucellosis, which was first introduced to the area by cattle in the 19th century. Brucellosis transmission between wildlife and livestock has been difficult to study due to challenges in culturing the causative agent, Brucella abortus . We examined B. abortus transmission between American bison ( Bison bison ), Rocky Mountain elk ( Cervus elaphus nelsoni), and cattle ( Bos taurus ) using variable number tandem repeat (VNTR) markers on DNA from 98 B. abortus isolates recovered from populations in Idaho, Montana, and Wyoming, US. Our analyses reveal interspecies transmission. Two outbreaks (2007, 2008) in Montana cattle had B. abortus genotypes similar to isolates from both bison and elk. Nevertheless, similarity in elk and cattle isolates from the 2008 outbreak suggest that elk are the likely source of brucellosis transmission to cattle in Montana and Wyoming. Brucella abortus isolates from sampling in Montana appear to be divided in two clusters: one found in local Montana elk, cattle, and bison; and another found mainly in elk and a bison from Wyoming, which is consistent with brucellosis having entered Montana via migration of infected elk from Wyoming. Our findings illustrate complex patterns of brucellosis transmission among elk, bison, and cattle as well as the utility of VNTRs to infer the wildlife species of origin for disease outbreaks in livestock.

Osteoblastomatosis of bone. A benign, multifocal osteoblastic lesion, distinct from osteoid osteoma and osteoblastoma, radiologically simulating a vascular tumor.

Two adult patients are described with multifocal osteolytic lesions radiologically simulating a vascular tumor. One patient had multiple bones involved. Histologically, the individual lesions had the features of the nidus of osteoid osteoma/osteoblastoma. A review of the English language medical literature yielded only one other reported case with similar features. The process is designated as osteoblastomatosis to indicate its bone-forming character, prominent osteoblast proliferation, and multiplicity. The cases are distinguished from multifocal/multicentric osteoid osteoma and osteoblastoma, and from benign and malignant vascular tumors.

Leg strength in peripheral arterial disease: associations with disease severity and lower-extremity performance.

OBJECTIVE: The purpose of this study was to determine relationships between lower-extremity arterial obstruction, leg strength, and lower-extremity functioning. DESIGN: The study design was cross-sectional. A total of 514 outpatients (269 with ankle-brachial index [ABI] <0.90), aged 55 and older, were identified from three Chicago-area hospitals. Individuals with history of lower-extremity revascularization were excluded. Main outcome measures Strength in each leg, 6-minute walk, 4-meter walking velocity, accelerometer-measured physical activity, and a summary performance score were measured. The summary performance score is a composite measure of lower-extremity functioning, ranging from 0 to 12 (12 = best). The leg with the lower ABI was defined as the "index" leg, and the leg with higher ABI was defined as the "contralateral" leg. RESULTS: Index leg ABI levels were associated linearly and significantly with strength for hip extension (P <.001), hip flexion (P <.001), knee extension (P =.066), and knee flexion (P =.003), adjusting for known and potential confounders. In adjusted analyses, the index ABI was also associated linearly and significantly with strength in the contralateral leg. Adjusting for confounders, including ABI, knee extension strength, was associated independently with functional measures. CONCLUSION: Among patients without prior leg revascularization, strength in each leg is highly correlated with the lower-leg ABI. Leg strength is associated independently with functional performance. Further study is needed to determine whether lower-extremity resistance training improves functioning in patients with peripheral arterial disease.